Topical application of estrogens has been known to prevent genital atrophy and to restore the normal state of the mucous membranes of the external genitalia. In view of this experiments have been carried on to determine the effect of estrogens in an ointment base in restoring normalcy to the senile skin. The experiments were carried out on five elderly patients, using estradiol and diethylstilbestrol, and with three additional patients as controls. Biopsies from nontreated areas showed the structure expected in senile skin. However, after topical application of estrogen-containing ointment the regeneration of the surface epithelium was pronounced. The number of cell layers was increased and the wavy configuration of the epidermis was restored. The water content of the estrogen-treated skin appeared greater and the elastic fibrils were more numerous. Biopsies from the skin of the control group showed no appreciable changes. This topical application affects the skin to a much greater degree than oral or parenteral application because the estrogen is not lost through body excretion, is not deactivated by the liver, and is not used preferentially by the genital tissues. It appears likely that estrogens may be used for the correction of pathologic changes in the skin other than those directly caused by estrogen deficiency.